DESCRIPTION (Applicant's abstract): The long-term goal of this study is to improve understanding of how information from peripheral mechanoreceptors involved in respiratory sensation and control is used by the central respiratory control processes in normal subjects and in patients with diseases that affect this information. These mechanoreceptors, distributed throughout the respiratory mechanical system, sense the degree and rate of mechanical deformation produced by breathing and external stimuli. This afferent information goes to brainstem processes that control the level and pattern of breathing and to higher brain cognitive processes. Since breathing is controlled at both subconscious (reflex) and conscious (behavioral) levels, and since both control modes depend upon mechanical information from the periphery, this afferent information determines the character of reflex and behavioral responses to mechanical stimuli in breathing pattern control. A central goal of the proposed research is to characterize this afferent information in normal human subjects by mapping on the scalp the temporal topology of short-latency components of the electroencephalogram evoked by small, brief negative pressure pulses applied at the mouth. These respiratory-related evoked potentials (RREPs) are distributed over the somatosensory cortex with location and timing dependent upon the specific site of sensation. Estimation of the cortical potential topology as a function of time post-stimulus will be done by computation of the scalp current density from the scalp potential distribution. This will establish the normal cortical potential pattern due to activation of the entire ensemble of mechanoreceptors, and we will evaluate influences of age and gender upon this pattern. In normal subjects, tests will be done to determine how this afferent activity correlates with cognitive perception of the stimulus by asking subjects to quantify their perceptions of the pressure pulse via crossmodality expression. In addition, subjects will be exposed to imperceptible mechanical loads in order to determine how they use mechanical information in reflexive control of their respiratory pattern. Normal subjects with temporary placement of a laryngeal mask airway will be tested to determine changes in the temporal topology of the RREP related to inclusion or exclusion of information from upper airway mechanoreceptors. Studies will be done in patients having a specific respiratory disorder that directly affects the nature of the afferent information: patients with double lung transplants, lacking information from some lung receptors, will be tested to determine how their RREP distribution differs from normals. These patients will also be tested to determine their cognitive perception of mechanical stimuli and their reflex responses to mechanical loading. The results of these studies will show the manner in which the various sources of peripheral afferent information, available for central control and cognition processes, project to the somatosensory cortex, and how this correlates with cognitive and control performances. These studies provide the basis for future examinations into how a variety of respiratory diseases may affect sensation, perception and control of respiratory processes in humans.